Method for combatting microorganisms



10 Claims. (Cl. 167-33) This application is a division of my application Ser. No. 248,302, filed Dec. 31, 1962, and now abandoned. The present invention provides a pest control agent containing, as the active ingredient, a thiazoline compound of the general formula in which R represents a phenyl radical which maybe substituted by one or several halogen atoms, trifluoromethyl groups, lower alkyl radical or alkoxy radicals, or by the chlorophenoxy radical, or represents the allyl radical or an alkyl radical with at most 18 carbon atoms, R represents a hydrogen atom, a lower alkyl radical or a lower dialkylamino group, R represents a hydrogen atom, a lower alkyl or a phenyl group, and R represents a hydrogen atom or the radical COOR Where R represents a lower alkyl radical, or-a salt thereof with an acid and, if desired, a diluent, a solvent, a wetting agent, an emulsifier, an adhesive, a fertilizer or a further pest control agent.

Especially valuable are those preparations which contain as active ingredient a compound of the above general Formula I in which R represents a phenyl group substituted by 1 to 2 trifluoromethyl groups, chlorine atoms, bromine atoms, lower alkyl or alkoxy groups or by the chlorophenoxy radical, min which R represents the allyl, dodecyl or octadecyl group. R represents a lower alkyl radical or the dimethylamino group, with the proviso that the substituents R and R at the two nitrogen atoms may replace each other, R represents a lower alkyl radical, or a hydrogen atom or the phenyl radical, and R stands for 'a hydrogen atom or the group or a salt thereof with an acid, more especially the hydrochloride, hydrobromide or perchlorate.

The synthesis of Z-imiriothiazolines may be carried out by one of the following known methods:

(a) Reaction of a monosubstituted thiourea with an with vxZfl-diChlOIOdlthYl ether to form 2-aminothiaz01e or a 2-imino-3 :4-thiazoline.

In the past, the aforementioned reactions were carried out in a polar solvent, for example water'or alcohol. However, it has proved advantageous to carry out the reaction in a non-polar solvent-,pr'eferably in toluene.

3,345,257 Patented Oct. 3, 1967 When the reaction solution is cooled, the corresponding halides.

The compounds of the general Formula I can be widely used for combating harmful organisms of the animal and plant kingdoms, for example they can be used for protecting plants, timber, a wide variety of industrial products and agricultural produce, as well as for protecting fibrous materials from harmful micro-organisms.

The new agents are suitable for combating harmful fungi, bacteria, acarides and insects and for controlling undesired plant growth.

As examples of the uses of the new compounds in plant protection there may be mentioned the treatment of plant seeds and of partially or wholly developed plants, and of the soil in which the plants grow, to protect them from harmful organisms, for example from harmful fungi, fungus spores, bacteria, nematodes and insects.

The compounds of the invention are especially suitable for combating genuine mildew, particularly in viniculture and horticulture, for example cucumber and apple mildew, and in this application the compound of the formula S-CH (lJ N-C-CHa proves especially efiicient.

A further sphere of use of the compounds of the Formula, I and of their salts is the control of undesired plant growth.

The active ingredients to be used as herbicides may be used by themselves or in conjunction with other weed killers, for example tri-substituted or tetra-substituted aryl-alkyl ureas, halogenated phenoxy:alkanecarboxylic acids, halogenated benzoic acids or phen-ylacetic acids, halogenated fatty acids or salts, esters or amides thereof, with borax or other inorganic salts, for example abraum salts, with calcium cyanamide, urea or other fertilizers, .or with pesticides, for example chlorinated hydrocarbons or phosphoric acid esters. They may also be combined with active compounds of basic reaction, for example tertiary or quaternary amines having a herbicidal effect. For example dodecyl hexamethyleneimine or salts thereof, or 1:1'-ethylene-2:2-dipyridilium dibromide. It is also possible to incorporate in the preparations herbicidally active carbamates or thiolcarbamates or dithiocarbamic acid esters or a derivative of s-triazine.

Other compounds suitable for incorporation are herbicidally active heterocyclic compounds, for example 2- chlorobenzthiazole, 3-amino-lz2z4-triazole, maleic acid hydrazide, 3:5 dimethyltetrahydro-1:3:S-thiadiazine-Z- thione, and also simpler herbicides for example pentachlorophenol, dinitrocresol, dinitrobutylphenol, naphthylphthalamic acid or methyl isothiocyanate. The new preparations may further contain identifying agents and further bactericides, fungicides and nematocides.

The new preparations may also be used in combination with fertilizers, for example in admixture therewith.

The preparations of the invention are suitable both for selectively killing weeds underneath culture plants and, when used in suitable concentrations, for the total killing off and destruction of undesired plant growth. Furthermore, the preparations of the invention display a fungicidal effect, for example on Aspergillus niger; a bactericidal effect, for example on Staphylococcus aureus; an insecticidal effect, for example on aphids or an ovicidal;

3 effect, for example on the meal moth (Ephestia Kiihniella).

For preparing solutions of the compounds of the general Formula I used as active principle for combating vegetable and animal pests, suitable for direct spraying there may be used, for example, organic solvents boiling above 100 C., such as diesel oil or kerosene, coal tar oils and oils of vegetable or animal origin, and also hydrocarbons for example alkylated naphthalenes, or tetrahydronaphthalene, if desired in combination with'xylene mixtures, cyclohexanols, ketones, also chlorinated hydrocarbons for example tetrachloroethane, trichloroethylene or triand tetra-chlorobenzenes.

When the compound to be used is soluble in water (for example in the form of one of its salts), aqueous forms of application are prepared by direct solution in water, or from emulsion concentrates, pastes or wettable spray powders by addition of water, Suitable emulsifiers or dispersants are non-ionic products, for example condensates from ethylene oxide with aliphatic alcohols, amines or carboxylic acids containing a long-chain hydrocarbon radical of about 10 to 30 carbon atoms, for example the condensation product from Octadecyl alcohol with 25 to 30 mols of ethylene oxide, Or soybean fatty acid with 30 mols of ethylene oxide, Or commercial oleylamine with 15 mols of ethylene oxide,

Or dodecylmercaptan with 12 mols of ethylene oxide.

From among the anionic emulsifiers that may be used there may be mentioned Suitable cationic dispersants are quaternary ammonium compounds, for example cet-yl pyridinium bromide, or dihydroxy-ethylbenzyl dodecyl ammonium chloride.

For the manufacture of dusting and scattering agents there may be used as solid vehicles talcum, koalin, bentonite, calcium carbonate, calcium phosphate, or coal, cork meal and wood meal or other materials of vegetable origin. It is also of great advantage to manufacture the preparations in the form of g-ranulates. The various forms in which the new compounds are used may contain the usual additives that improve the dispersion, adhesion, stability towards rain or the penetration. As such substances there may be mentioned fatty acids, resins, glue, casein or, for example, alginates.

Another object of the present invention are the new compounds of the general formula in which R represents an allyl radical, the dodecyl radical or a phenyl radical substituted by at least 2 halogen atoms or lower alkyl groups or by one or several trifluoromethyl groups or by lower alkoxy groups or by the chlorophenoxy radical, R represents a hydrogen atom, a lower alkyl group or a lower dialkylamino group, with the proviso that the substitutents R and R at the two nitrogen atoms may replace each other, R represents a hydrogen atom, a lower alkyl radical or a phenyl group, R represents a hydrogen atom or the radical --COOR where R represents a lower alkyl group, or their salts with acids, as well as processes for the manufacture of these new compounds by as such known methods.

The following examples illustrate the invention, the parts and percentages being by weight.

4 EXAMPLE 1 OFQ was prepared in the following manner:

A suspension of 8|l.5 g. of N-(3:5-di-trifluoromethylphenyl)-N'-methylthiourea in 2 to 4 times its own weight of toluene was heated to 90 C. to 25 g. of chloracetone were then added dropwise and stirred in while a rise in temperature was observed and droplets of water were formed. When all had been added, the reaction was completed by stirring the mixture for 15 minutes at the boil. The mixture was then allowed to cool, whereupon the hydrochloride of the reaction product settled out in the form of a viscid oil which quickly solidified when the wall of the vessel was scratched with a glass rod. The toluene was removed from this crystalline mass, the residue taken up in a small amount of hot alcohol and the solution was filtered. Ether was added to the warm alcoholic filtrate until a slight turbidity appeared, and the batch was then kept in a refrigerator, whereupon the hydrochloride of the reaction product settled out in pure form as an almost colorless, faintly yellowish crystalline substance which was filtered off, washed with ether and dried under vacuum.

The yield of hydrochloride was 65% of the theoretical yield; a further amount of the product can be obtained from the mother liquors on addition of ether.

The transformation of the hydrochloride into the free base was achieved as follows: 1 part of the hydrochloride was stirred with 1 part of water and 3 to 4 parts of ether. A slight excess of approximately 3-normal sodium hydroxide solution was added dropwise to this mixture, and the ethereal layer was separated in a separating funnel, dried over sodium sulfate and the ether was evaporated; the residue was then recrystallized from dilute alcohol.

Hydrochloride Free base 219-223" C. with 87' G.

decomposition.

Analysis Ol3HllN2Cls 0--- ciaHioNzs e- Calculated 7.44% N 45.88% C; 2. 6% H; 8.23% N. Found 7.67% N 46.2% 0; 3.0% H; 8.2% N.

Melting point S-CH by reacting 100 g. of N-para-chlorophenyl-N-methylthiourea with 41 g. of chloroacetone.

Hydrochloride Free base (XlHzO) 193-195" C 6768 o. gCglifioNzChsnn gulgyhgcls. 7 H 7 N o 5.3 ;4.64 11.73 Found 96%N 55.1472; 4.62%; i1.94%. 0

Yield of hydrochlorides: of the theoretical.

(3) 2 (meta trifluoromethylphenyl) -imino-3:4-dimethylthiazoline of the formula S-OH V H: from 58.5 g. of N-meta trifluoromethylphenyl-N-methylthiourea and 26.5 g. of chloracetone. 1

from 60g. of N- phenyl-N'-methylthiourea and 33.3 g. of

chloracetone. Yield of hydrochloride: 87% of the theoretical.

Melting point, 72-74. I Analysis.-C H N S. Calculated: 64.67% C; 5.92%

H; 13.71% N. Found: 64.54% C; 5.94% H; 13.55% N.

(5) 2 (3:4 dichlorophenyD-imino-3:4-dimethylthiazoline of the formula /S -CH u N-C-CH: 01 I H from 90. g. of 3:4-dichlorophenyl-N-methylthiourea and 35.2 g. of chloracetone. Yield of hydrochloride: 87% of the theoretical.

Hydrochloride Free base Melting point 193205 C. 68. 5-69. 5 C. Analysis CuHuNzSCls CnHmNzChS C H N C H N Calculated, percent 42. 67 3. 58 9. 05 48. 36 3. 69 10. 25 Found, percent 43. 0 3. 7 9. 1 48. 16 3. 76 10. 48

(6) 2-allylimino-3 :4-dimethylthiazoline of the formula s-on CH =CHCHr-N=O III-C-CH: CH3

from 60 g. of N-allyl-N'-methylthiourea and 42.5 g. of chloracetone in 150 ml. of toluene. Yield: 72% of the theoretical.

Boiling point: 80 C. under 0.04 mm. Hg'pressure.

AnalysisreC H N s. Calculated: 16.65% N. Found: a

(7) 2 (meta trifluoromethylphenyl)-imino-3-ethyl-4- methylthiazoline of the formula CH -CH;

N-C-CHa s-on from 100 g. of N-3-trifiuoromethylphenyl-N'-ethylthiourea and 41.2 g. of chloracetone in 200ml. of toluene.

. Yield of hydrochloride: 77% of the theoretical.

6 Melting point: 183-193 C. A is .--C1 3H14N2C1SF3. Calculated: .5 4.35% H; 8.7% N. Found: 48.8% C; 4.4% H; 8.6% N. (8) 2 (3 :4 dichlorophenyl)-imino-3-ethyl-4-methy1- thiazoline of the formula from 24.9 g. of N-3 :4-dichlorophenyl-N'-ethylthiourea and 9.5 g. chlor-acetone in 100 m1. of toluene.

Yield of hydrochloride: 24g.

Melting point: 170176 C.

Analysis.C H N SC1 Calculated: 44.53 C; 4.05% H; 8.66% N. Found: 44.60% C; 4.13% H; 8.61% N.

(9) 2 (3t4 dichlo1'ophenyl)-imino-3-methylthiazoline of the formula S-CH -N=IC\ N-CH 01 l CH3 frorn BO g. of N-3;4-dichlorophenyl-N'-methylthiourea and 18.5% g. azfi-dichlorodiethyl-ether in 100 m1. of aqueous toluene.

Yield of hydrochloride: 20 g.

Melting point: 1911-199 C.

Analysis. CmHgNgSClg.

Calculated: 9.48% N;

----10.85% S. Found: 9.50% N;-10.79% S.

(10) 2 phenylimino S-dimethylamino 4-methylthiazoline of the formula III-CH-CH:

' from 24 g. of l:1-dimethyl-4-phenylthio-semicarbazide andy 12 g. of chloracetone in n-propanol, precipitated by adding ether.

Yield of hydrochloride: 24.5 g.

Melting point: 176-l1-91 C. 7

Analysis. C N N SCl. Calculated: 53.42% C; 5.98% H; 15.58% N. Found: 53.42% C; 6.29% H; 15.51% N.

(11) 2 meta trifluoromethylphenyl-imino-3-methylthiazoline of the formula 1 i N- H from 30 g. of N-meta-trifluoromethylphenyl-N-methylthiourea and 18.5 g. of lzzdichlorodiethyl ether in ml. of aqueous toluene.

Yield: 23 g. of thiazoline free from hydrochloric acid, boiling at 138-439" C. under 0.03 mm. Hg pressure.

- Analysis.C H N SF Calculated: 51.16% C; 3.51%

H; 10.85% N. Found: 50.90% C; 3.48% H; 10.60% N. (12) 2-phenylimino-3-isopropyl-4-phenylthiazoline of the formula on oh, on.

from 23.4 g. of N-phenyl-N'-isopropylthiourea and 23.9 g.

of phenacylbromide in 100 m1. of toluene.

Hydrochloride heses) N- 48.42% C; 4.69% H:

found (calculated values in parent /sGCOOCaHr C N-G-CH:

Percentage Thiazollne s9-91 137-145" C. CuHrsOzNiSCl 54.10% C; 4.86

Melting Point,

from 30 g. of N-me'ta-chlorophenyl-N'-methylthiourea and 24.6 g. of monochloroacetic acid ester.

Yield: 47% of thiazoline free from hydrochloric acid.

Calculate The following compounds are accessible in a similar ide melting at 196200 C. (14) Z-(meta-chlorophenyl)-imino 3:4 di-mthyl-S- Calculated: 57 60% C; carboxyethylthiazoline of the formula /SCH -N-C\ NCCHa DA/Ie1t1ing pointfrom hydrochloric acid, na yslsmm" elting 12.83% N. manner:

Formula SCCOOO2H5 m 0 0 0 we 4 mu m n m u m 9 m P 9 1 1 H 0 m 0 H s clllll H 0 s a N 1 0 0 1 0 m u n 6 1 Yield: 37 g. of hydrobrom c1gH19N2 SBI'. V 5.10% 7.46% N. Found: 57.45% C; 7.47% N.

-(13) 2 (meta-toluyl)-imino-3 :4-diinethylthiazoline o 5 the formula from 36 g. of N-meta-toluyl-N'-methy1thiourea and 18.6 g. of chloracetone.

Yield: 20 g. of thiazoline free boiling at 156 C. under 0.2 mm. Hg pressure, n1 at4850 C.

Analysis.'C H N S. Calculated: 66.02% C; 6.46% H; 12.83% N. Found: 65.90% C; 6.43% H;

in parentheses) Percentages found (calculated values Melting Point, C.

N-CH Formula S'OH .HClO4 N-C-OHs 1 With decomposition.

Percentages found (calculated Melting values in parentheses) Formula P0016115, Boiling Point, C. 1

' o H N /SCH 22- Cl-QN: .1101 1233 46.15 3. 79 10. 55 (45. 99) (3. 86) (1O. 73)

III-OH CH s-Cu 23------ CH (GHz)i1-N=O 1- 148-150, 0.04 mm--. 10.5

(10.43) N-CH /S-CH 24-.---- OH3 (CH2)I1N=O 130, 0.03 mm--.- 68.7 10.9

lITC-OH3 CH3 1 With decomposition. 4

' Percentages found (calculated values in Melting parentheses) Formula Point,

O H N /SCH 25 Br-Q .HOl 211-213 22 .1 10) (3:2)

. 8 N(|]H CH3 CH3 /SOH 26 oiH,0-N=o 011 63.8 7.0 10.4

(64. 09) (6. 92) (10. 68) IITCH V 1 S OH CH3 CH3 /S CH 28 o1- =o .HBr 235-238 46.3 3.3 6.8

l CH

1 With decomposition.

EXAMPLE 2 EXAMPLE 3 (a) A wettable powder Was prepared containing of the active principle mentioned under (1) in Example 1 (used in the form of its hydrochloride), as well as 80% of a mixture of kaolin, finely dispersed silicic acid and an emulsifier mixture consisting of the sodium salt of dodecyl alcohol sulfuric acid ester and an adduct from ethylene oxide and tertiary octylphenol. The mixture can be di luted in any desired proportion with water, whereupon it forms a stable dispersion.

(b) A solution of 20 parts of the compound (5) of Example 1 in parts of xylene was mixed with 10 parts of a dispersing and emulsifying agent consisting of a mixture of the sodium salt of dodecyl alcohol sulfuric acid ester and an adduct from ethylene oxide and tertiary octylphenol. The solution can be mixed with water in any desired proportion to form a milky dispersion.

amount of 0.2% of active principle.

F ungiciaal action (a) cotyledons of Cucumis pep'o were treated with a spray broth as described in Example 2(a) containing 0.2% of the active principle described in Example 1 (under 1).

6 5 2 days after the treatment, these cotyledons were infec-ted with spores of Erysiphe cichariacearwm.

12 days after the infection, it was observed that the plants treated with the' spray broth according to Example 2(a) were not attacked by powdery mildew, whereas the 70 untreated control plants were strongly infected.

1 '1' EXAMPLE 4 H erbicidal action A. PRE-EMERGENCE The following types of plant were grown in pots in a greenhouse: Setaria italica, Sinapis alba, Medicago sativa, Lepidium sativum and Calendula chrysantha. 2 days afterwards the surface of the earth in the seeded pots was treated with an emulsion according to Example 2(b), the amount of active principle used being equivalent to 10kg. of active principle per hectare. 3 weeks after the treatment, the aforesaid plants had either not germinated at all or had died off completely after germination. Medicago was so much damaged that normal further development had become impossible.

' B. POST-EMER GEN'CE Earthenware pots were prepared as described under (a) above and "seeded with the same kinds of plant. The treatment with the same active principle as under (a) used in an equal amount was carried out when the plants had developed the first pair of true leaves, that is to say about 9 to 11 days after seeding. 3 weeks after the treatment, all the aforementioned types of plant had died off completely.

Good effects against Weeds were also achieved by using spray broths as described under (a) or (b) above which contained one of the following compounds described in Example 1: 2, 3, 4, 6, 8, 9, 11, 13, 15 to 20, 22 to 28.

- What is claimed is:

1. The method for combating harmful microorganisms,

wherein there is applied to the areas whereon the micro-- organism combating effect is desired, a biocidal amount of a member selected from the group consisting of (A) a compound of the formula wherein R is a member selected from the group consisting of (a) phenyl, phenyl substituted in at most 2 places by a member selected from the group consisting of chlorine, CF lower alkyl, lower alkoxy and chlorophenoxy, (b) allyl and (c) alkyl with at most 18 carbon atoms, R is a member selected from the group consisting of hydrogen, lower alkyl and lower dialkylamino, R is a member selected from the group consisting of hydrogen, lower alkyl and phenyl, R is a member selected from the group consisting of hydrogen, and -COOR where R is lower alkyl, and (B) a salt of a compound set forth above under (A) selected from the group consisting of hydrochloride, hydrobromide and perchlorate.

2. A method as claimed in claim 1, wherein there is used a biocidal amount of the compound of the formula 3. A method as claimed in claim 1, wherein there is used a biocidal amount of the compound of the formula 12 4. A method as claimed in claim 1, wherein there is used a biocidal amount of the compound of the formula 5. A method as claimed in claim 1, wherein there is used a biocidal amount of the compound of the formula 6. A method as claimed in claim 1, wherein there is used a biocidal amount of the compound of the formula 7. A method as claimed in claim 1, wherein there is used a biocidal amount of the compound of the formula 8. A method for combating harmful fungi wherein there is applied to the area whereon the fungi combating effect is desired, a fungicidal amount of the compound of the formula CFa 9. The method for combating insects, wherein there is applied to the areas whereon the insect combating effect is desired, an insecticidal amount of a member selected from the group consisting of (A) a compound of the formula wherein R is a member selected from the group consisting of (a) phenyl, phenyl substituted in at most 2 places by a member selected from the group consisting of chlorine, CF lower alkyl, lower alkox'y and chlorophenoxy, (b) allyl and (c) alkyl with at most 18 carbon atoms, R is a member selected from the group consisting of hydrogen, lower alkyl and lower dialkylamino, R is a member selected from the group consisting of hydrogen, lower alkyl and phenyl, R is a member selected from the group consisting of hydrogen, and COOR where R is lower alkyl, and (B) a salt of a compound set forth above under (A) selected from the group consisting of hydrochloride, hydrobromide and perchlorate.

10. The method for combating acarides, wherein there is applied to the areas whereon the acaricidal combating effect is desired, an acaricidal amount of a member selected from the group consisting of (A) a compound of the formula wherein R is a member selected from the group consisting of (a) phenyl, phenyl substituted in at most 2 places by a member selected from the group consisting of chlorine, CF lower alkyl, lower alkoxy and chlorophenoxy, (b) allyl and (0) alkyl With at most 18 carbon atoms, R is a member selected from the group consisting of hydrogen, lower alkyl and lower dialkylamino, R is a member selected from the group consisting of hydrogen, lower alkyl and phenyl, R is a member selected from the group consisting of hydrogen, and -COOR Where R is lower alkyl, and (B) a salt of a compound set forth above under (A) selected from the group consisting of hydrochloride, hydrobromide and perchlorate.

1 4 References Cited UNITED STATES PATENTS 1,961,840 6/1934 Bolton 167-33 2,902,356 9/1959 Luckenbaugh 7l2.5 3,119,831 1/1964 Homer 712.5 X

OTHER REFERENCES Hunter et 211., J. Chem. Soc. (London), 1934, pp. 1175 to 1177.

0 ALBERT T. MEYERS, Primary Examiner.

J. O. THOMAS, S. ROSEN, Examiners.

S. FRIEDMAN, Assistant Examiner.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3,345,257 October 3, 1967 Dieter Duerr et al.

It is hereby certified that error appears in the above numbered patent requiring correction and that the said Letters Patent should read as corrected below.

Column 4, line 14, before "25" strike out "to"; lines 56 to 61, the formula should appear as shown below instead of as in the patent:

S---CH Cl N:C

N C CH line 75, for "hydrochlorides" read hydrochloride column 11, lines 60 to 65, the formula should appear as shown below instead of as in the patent:

3 /scH I? C CH CF Signed and sealed this 22nd day of April 1969.

(SEAL) Attest:

EDWARD M.FLETCHER,JR. EDWARD J. BRENNER Attesting Officer Commissioner of Patents 

1. THE METHOD FOR COMBATING HARMFUL MICROORGANISMS, WHEREIN THERE IS APPLIED TO THE AREAS WHEREON THE MICROORGANISM COMBATING EFFECT IS DESIRED, A BIOCIDAL AMOUNT OF A MEMBER SELECTED FROM THE GROUP CONSISTING OF (A) A COMPOUND OF THE FORMULA 